13 research outputs found
The effect of Arginine on gastric cancer cell behaviour : molecular mechanisms of action
No full textThe effect of arginine on gastric cancer cell behaviour: Molecular mechanisms of action – Abstract of thesis In gastric cancer patients undergoing surgical resection, the immunosuppression associated with surgery together with the malnutrition, which these patients often have, contribute substantially to a 40% risk of major peri-operative morbidity. Standard nutritional support in these patients has had mixed results. However, the ingestion of key nutrients, which modulate immune, inflammatory and metabolic pathways, also known as immunonutrition, offers a therapeutic modality, by reducing infectious complications by approximately 50%. However, studies have shown that arginine a key nutrient included in immunonutritional regimens not only has immune-enhancing effects but also has the ability to both stimulate and inhibit tumour growth. Therefore concerns remain with regard to the peri-operative use of arginine with regard to tumour growth and dissemination around the time of surgery. The aims of this study were to evaluate the in vitro effects of arginine on gastric cancer cell growth and invasion and the potential molecular mechanisms underlying any changes. A feasibility study was conducted to evaluate the influence of immunonutrition on gastric cancer patients by way of effect on expression of genes involved with tumour growth and invasion. The in vitro data confirmed that both stimulation of apoptosis associated with an increase in caspase 8 expression and cell cycle arrest at G2 phase independent of the effects of both p21 and p53 were associated with inhibition of AGS cell growth. No significant effect on invasion was demonstrated on AGS cells treated with arginine. The feasibility study demonstrated the challenges associated with extracting adequate quantity and quality of RNA from gastric tumour tissue. However, a total of 668 genes demonstrating a two fold change in gene expression were identified in the gastric tumour biopsies following feeding with immunonutrition. In summary, our data confirms inhibition of gastric cancer cell growth with arginine supplementation. However, the peri-operative use of arginine enriched nutritional support in patients with gastric cancer requires further assessment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Preservation of small bowel with the selective use of heparin and second look laparotomy in acute mesenteric ischaemia: A case report
No full textAbstractIntroductionAcute mesenteric ischaemia may occur due to mesenteric arterial embolus, thrombosis, non-occlusive mesenteric ischaemia or venous thrombosis resulting in ischaemia of the bowel wall.Presentation of caseA 41year old woman presented with worsening abdominal pain, decreased appetite, nausea and vomiting. Examination revealed right lower quadrant tenderness. Investigations revealed elevation of her inflammatory markers. At laparotomy two separate segments of ischaemic but potentially viable small bowel were identified secondary to mesenteric venous thrombosis. Bowel salvage was attempted with the use of intravenous unfractionated heparin and this was confirmed following a second look laparotomy.DiscussionDespite a normal platelet count at presentation a diagnosis of JAK-2 positive essential thrombocythaemia was made thus explaining the acquired prothrombotic state underlying the venous thrombosis. The selective use of intravenous unfractionated heparin and second look laparotomy may provide a means for bowel preservation in these cases.ConclusionThis case highlights the potential of bowel salvage can be achieved following an episode of acute mesenteric ischaemia with the use of intravenous unfractionated heparin and selective second look laparotomy and the importance of considering underlying myeloproliferative disease in such cases even in the absence of a thrombocytosis at presentation
Optimal gastric pouch reconstruction post-gastrectomy
No full textBackground. Gastric pouches have the potential to improve nutrition following total gastrectomy, compared with standard reconstruction. However, a consensus view of clinical benefit is not available, at least partly due to a lack of standardization of pouch design or size. This study was undertaken to identify optimal conditions for pouch design. Methods. A mathematical model was established and a porcine model constructed to evaluate the pressure/volume dynamics of the pouch. A "J" pouch was constructed at anastomotic lengths of 5, 10, 15, and 20 cm. Each pouch was distended with saline and the pressure/volume relationship established. Results. Mathematically, increasing the anastomotic length of the pouch to 15 cm increases the volume significantly; thereafter, there is minimal benefit of increasing the pouch length further. For smaller pouches (5 and 10 cm) a 350-to 400-ml volume (approximate meal volume in the elderly) is never achieved until higher pressures (45 cmH O) are applied. However, in the larger pouches (15 and 20 cm) a 350-to 400-ml volume is readily achieved at basal pressures of 15 cmH O. Conclusion. Smaller pouches never achieve adequate volumes at basal pressures; accordingly, it is unlikely that they will lead to any clinical benefit. Further in-vivo studies should therefore be based upon 15-cm pouch designs
Prognostic Value of Computed Tomography : Measured Parameters of Body Composition in Primary Operable Gastrointestinal Cancers
No full textProfessor Graeme Murray, Department of Pathology, University of Aberdeen provided us access to the colorectal cancer pathology databases from which the colorectal component of the research was based. Conflict of interest There are no conflicts of interest.Peer reviewe
Erratum: Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas
No full textCorrection to: Corrigendum: British Journal of Cancer (2015) 113, 1641–1641. doi:10.1038/bjc.2015.391; published online 1 December 2015 Upon publication of the above corrigendum in the British Journal of Cancer, the authors noted that author KM Matula had been placed in the incorrect position on the author listing. The publishers would like to apologise for this mistake. The full and correct author listing is reproduced above
Optimized response prediction in esophagogastric junction adenocarcinomas (EGJAc) with combination of molecular biomarkers and FDG-PET.
No full text 1 Background: Predictive biomarkers (BMs) for EGJAc would optimise treatment selection and avoid ineffective therapy. Metabolic response (MR) defined as >35% decrease in tumour FDG Standardized Uptake Value (SUV) between day 0 & 14 after starting chemotherapy has a high negative predictive value (95%) for response, but limited positive predictive value (50%). Combining molecular BMs with FDG-PET may optimise response prediction. We used global gene expression profiling (GEP) to identify molecular BMs that when combined with FDG-PET would improve predictive accuracy. Methods: 28 patients with locally advanced or metastatic EGJAc received platinum based chemotherapy (PBC). FDG PET CT scans were at day 0 and day 14 and GEP (Affymetrix ST1.0 Exon Genechips) on day 0 tumour biopsies. A tissue microarray comprising an independent set of 154 OGJAc who underwent surgery +/− neoadjuvant PBC was used with immunohistochemistry (IHC) for qualification of GEP results. Radiological response was assessed after 3/ 4 cycles of PBC by RECISTv1.1. Results: We identified a gene expression signature (86 genes) that separated FDG PET MR patients(>35% fall SUV day 0 to14) into those that do and do not go on to have a RECIST response. In cross validation, this signature correctly predicted response in 28/28. Pathway analysis on GEP data identified potential novel mechanisms of response, including the Leptin pathway. Leptin mRNA was higher in FDG metabolic responders who did not have a RECIST response compared to those that did. In the independent set, high Leptin protein by IHC was strongly associated with lack of histopathologic response to neoadjuvant PBC (n=64, p=0.002). High Leptin expression also had a therapy independent prognostic effect with longer survival in the absence of histopathologic response or with no neoadjuvant PBC and in low Leptin patients poor survival was mitigated to a certain extent by neoadjuvant PBC (n=154, Kaplan-Mieier, log rank p=0.041 & Cox MVA p=0.040). Conclusions: Molecular biomarkers (Leptin in particular) combine with FDG PET to optimise response prediction in EGJAc. Further investigation of this combined molecular and imaging approach is warranted. </jats:p
Surgical site infection after gastrointestinal surgery in children: An international, multicentre, prospective cohort study
No full textSurgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings
Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries
No full textBackground: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars (216 compared with 6 (95% confidence interval [CI]: −1) difference in costs. In India, the average cost for high FiO2 was 195 for low FiO2 leading to a −15 to −1164 compared with 93 (95% CI: −65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this
